June, 1946
937
1,5,3,6-DIANHYDROMANNITOL AND ISOMANNIDE
dinitrophenylhydrazone, melting a t 162-163 *. The quarktity was not considered significant.
TABLE I OF 3,3‘-D~ENZOn-2,2’-DI-(D-GLYCERALDE3,3’-Dibenzoyl-2,2‘-di-(~-glyceraldehyde)Ether Dihy- DISPERSION drate.-A solution of 50 CC. of glacial acetic acid containing HYDE) ETHER DIHYDRATE 1 g. (0.0027mole) of 2,5-monoanhydro-1,6-dibenzoylsorl~i- 0.1222g. dissolved in 4 cc. of 95y0 ethyl alcohol in a 2to1 and 1.8g. (0.0041 mole) of lead tetraacetate was allowed decimeter tube (equivalent t o 3.055g. in 100 cc.) to stand at mom temperature for twenty-four hours. The Temperature = 31.5’ mixture was then treated with hydrogen sulfide and the
precipitate of lead sulfide was removed. The filtrate was aerated t o remove hydrogen sulfide and was treated with 1 N potassium hydroxide solution until the first signs of permanent turbidity persisted upon shaking. The solution, still acid to litmus, was put away in the refrigerator. Long, colorless needles were deposited overnight. The crystals were filtered off, dissolved in a little ethyl alcohol, and precipitated by the careful addition of water t o incipient turbidity. Two more recrystallizations from alcohol and water yielded colorless needles melting at 124-126’ (cor.). In another experiment the filtrate, after removal of lead sulfide, was concentrated in vacuo at 40” t o a thin s h i p . Water (40 cc.) was added followed by the careful addition of alcohol. Upon vigorous shaking the sirup disappeared and a colorless, crystalline product was deposited. $!ecrystallization was effected from a mixture of benzene and petroleum ether. Colorless, feathery needles, melting at 124-126”,which did not depress the melting point of the previous compound were obtained. The yield was 0.68 g. or 61%. No derivatives could be obtained with methone reagent, phenylhydrazine or 2,4-dinitrophenyl-tiydrazine. Two per cent. solutions of the compound in ethyl alcohol, glacial acetic acid and chloroform exhibited no rotation. A molecular weight determination by fre1.zing-point depression of benzene gave a value of 386 (calcd. 406). This measurement is sufficiently accuritte t o show that cleavage of the original substance into fragments did not occur. Anal.lo Calcd. for GHsOQ: C, 59.11; H, 5.41. Found: C,59.0,59.2; H , 5.24,5.09. The rotations observed a t all wave lengths utilized were within the range of cxperimental error.
Metal Wavelength Reading
Red
Yellow
Cd
Na
THE
Cu
Hg
Cu
Blue
Cd
6438 6890,9f3 5700 5461 5106 4800 0.01 0.00 0.00 0.00 0.02 0.01
Rates of Oxidation.-The acetic acid was prepared exactly as that described by Hockett, Dienes and Ramsden.’ The standardized’ conditions described by them were used for the rate determinations.
Summary The preparation of a compound previously designated by Brigl and Griiner as 2,5-monoanhydro-1,fi-dibenzoylmannitol has been repeated by their method of direct anhydridization of 1,6dibenzoylmannitol. By debenzoylation of this product we have obtained also a monoanhydrohexitol. The behavior of these compounds when oxidized by lead tetraacetate shows that the 2,5ring is present, but the observation that the resulting 3,3’-dibenzoyl-2,2’-di-(D-glyceraldehyde) ether dihydrate is optically inactive in three solvents and toward six wave lengths of light proves that a Walden inversion occurred during anhydridization and that the anhydrohexitol must be 2,5-monoanhydrosorbitol rather than 2,5-anhydromannitol. CAMBRIDGE, MASSACHUSETTS
RECEIVED JANUARY 29, 1946
(10) Analysis by Mrs. C. K. Fitz, M. I. T.
[CONTRIBUTION FROM
Green Green Green
SUGAR RESEARCH FOUNDATION LABORATORY AND FROM MASSACHUSETTS IlrTSTITuTE OF TECHNOLOGY]
THE
DEPARTMENT OR CHEMISTRY
Hexitol Anhydrides.’ The Preparation and Proof of Structure of 1,5,3,6Dianhydromannitol (Neomannide) The Structure of Isomannide*
.
BY
R.
c. HOCKETT~ AND ELIZABETH L.SHBFFIELD
In the preceding paper of this series, it was thesis of the 1,5,3,6-dianhydride by a method shown that Fauconnier’s crystalline “isomannide” analogous to that introduced by Fischer and is either 1,5,3,6- or 1,4,3,6-dianhydramannitol. Zach6 for the preparation of methyl 3,6-anhydroSince styracitol has recently been shown to be 1,5- D-glucopyranoside. The first two steps of this proposed synthesis mon~anhydromannitol~ we considered this substance to be a suitable starting material for syn- had already been carried out successfully by Zervas and Papadimitriou,* who obtained a (1) The previous paper of this series, THIS JOURNAL, 68, 935 crystalline 6-tosyl-2,3,4-tribenzoylstyracitol.The (1946). (2) The material in this paper is taken from a thesis submitted to presence of the tosyl group in the six position is the Graduate School of the Massachusetts Institute of Technology in indicated not only by the numerous analogous partial fulfillment of the requirements for the degree of Doctor of cases where selective tosylation has been carried Philosophy by Elizabeth L. Sheffield in October, 1944. The paper was read before the Division of Sugar Chemistry and Technology at out upon substances containing both primary the New York meeting of the American Chemical Society in Sep and secondary hydroxyl groupsI6but likewise by tember, 1944. (3) Present address: Sugar Research Foundation, 52 Wall St., New York, N.Y. (4) Zervas and Papadimitriou, Bcr., OS, 174 (1940); cf. Hockett and Conley, THISJOURNAL, 66, 404 (1944); cf. Richtmyer, Cam and Hudson, ibid., 66, 1477 (1943).
(5) Fischer and tach, Bcr., 46, 456, 2068 (1912); cf. Hockett, Nickerson and Reeder, Tars JOURNAL, 66. 472 (1944). (6) Compton. ibid., 60,395 (1938); Hockett and Downing, ibid., 64,2463 (1942); cf. Brigl and Griiner,Ba.. 66, 641 (1932); also UQpublished results.
R.C. HOCKETT AND ELIZABETH L.SHEFFIELD
938
HOCH
I I Limited HOCH 0 tosylchlaide HOCH
'A
Benzoyl
1 1
HC
HCI HiCOTs 6-Tosylstyracitol (not isolated)
I H&OH
Styracitol
0
BzOCH
I
0
1 1 1
HCOBz
-
NaOCH,
I
r-CH
I 0
I ~ C H I O H HCOH
HC--
IJ
0
I
or
I HC
I L-CH? I HiCOTs 2,3,4-Tribenzoyl-61,5,3,6(1,4,2,6)tosylstyracitol Dianhydromannitol (2,3,4-Tribenzoyl-6( Neomannide) tosyl-l,5-anhydromannitol) I
1,5,2,6Dianhydromannitol
I1
1,5,4,6(1,3,2,61Dianhydromannitol I11
the rate a t which replacement of tosyloxy by iodide takes p i ~ e . 4 We were able to duplicate the preparation and obtain the substance described by these authors. On treating the compound with methanolic sodium methylate, we obtained a substance without benzoyl groups and corresponding in composition to a dianhydromannitol. It proved to be a new cornpound not identical with any of the known mannides.' . We designate this compound as neomannide. TABLE I M. p.,
6-Mannide Isomannide
119 87
OC.
D I . [
(HnO)
Author
+94.05 ' +90.9"
Siwolobow" Hockett, etal! Fauconnier' Mannide .. . . . Berthelotd Neomannide 112.8-113.3 6.4' Hockett and (cor.) Sheffield Siwolobow, Ann., 233, 368 (1886). Reference 1. Fauconnier, BdZ. soc. chim., (2) 41,119 (1884). Berthelot, Ann. chim., (3) 47, 312 (1856).
+
...
The method of preparation of neomannide limits the possible structures to the three (I, 11, 111) shown in the equations, since the 1,5ring pre-
VOl. 68
existed and conditions were too mild to cause any shift. Since neomannide is not attacked by lead tetraacetate, structures I1 and I11 are eliminated and only the 1,5,3,6(1,4,2,6) remains (I). The possibility of a Walden inversion at carbon three is very remote for the reasons discussed in an analogous case.? Therefore neomannide is 1,5,3,6-dianhydromannitol. This structure is consequently eliminated for isomannide, which is not identical with neomannide, and the only probable structure remaining for isomannide is 1,4,3,6-dianhydromannitol,which was selected as one of two possibilities in the preceding paper.' Acknowledgment.-The authors wish to acknowledge the advice and counsel of Dr. R. Max Goepp, Jr., of the Atlas Powder Co. throughout this investigation. Experimental Styracito1.-This compound was prepared by the method of Maurer and Mahn* as modified by Hockett and Conley.' Our product melted a t 153.1-154.3' (cor.). 6-Tosyl-2,3j4-tribenoylstyracitol.-Styritol (5 g., 0.031 mole) was suspended in 50 cc. of pyridine and tosyl chloride (5.8 g., 0.031 mole) was added. The mixture was shaken until solution was complete and left for one hour at room temperature. It was then cooled t o -5' and benzoyl chloride (17.6 g., 0.11 mole) was added. The ' 0 for two hours and then at room maxture was kept at . temperature for three hours. Ice water (100 cc.) was added and a sirup separated. The water was decanted and the sirup treated with ten 50-cc. portions of hot water containing a few drops of acetic acid. The crude product separated crystalline from a mixture of 100 cc. of reagent alcohol and 2 cc. of acetic acid. The yield was 8.5 g. or 47% of the theoretical quantity of crystals melting at 161.4-162.7'. Zervas and Papadimitriou' give 162'. 1,5,3,6-Dianhydromaaaitol (Neomannide).-Sodium (0.8 g., 0.034 mole) was dissolved in 200 cc. of dry methanol, by warming under reflux for five minutes and then cooling t o room temperature. T o the sodium methylate solution was added 20 g. (0.032 mole) of 6-tosyl-2,3,4tribenzoylstyracitol. The mixture was boiled under reflux for two hours. The styracitol ester dissolved in the first fifteen minutes. The mixture was cooled, neutralized t o phenolphthalein with 10% sulfuric acid and filtered. The filtrate was evaporated dry under diminished pressure and the residue extracted with three 100-c~.portions of hot ethyl acetate. After 24 hours at 0" the combined extracts deposited crystals (0.7 g.). By concentrating t o 50 cc. and cooling, a total of 2.9 g. or 63% of the theoretical yield of product was obtained. The melting point was initially 109.1110.9' but rose to 112.8-113.3° (cor.) after two recrystallizations from 45-55-cc. portions of ethyl acetate. Further recrystallization was without effect on the meltingo point. The substance showed a specific rotation of +6.40 (c, 2.93 or 5.65; HzO; 22'; D line of sodium). Anal. Calcd. for GHIoO,: C, 49.25; H, 6.87. Found: C, 49.00, 49.10; H, 6.94, 6.90. Oxidation of Neomannide by Lead Tetraacetate.-The conditions described by Hockett, Dienes and Ramsden' were used, but no consumption of the oxidant occurred.
summary The preparation of a new dianhydromannitol, (7) Hockett, Conley, Yusern and Mason, Tms JOURNAL, 68, 922 (1940). (8) Maurer and Mahn, Bn.,SO, la10 (1927). (9) Hockett, Dienes and Romsdtn, Tsra JOVW&L. 66. 1474 (i94a).
June, 1946
1,4,3,6-DIANHYDRO-L-IDITOLj ISOMANNIDE AND
neomannide, is described and its structure determined as 1,5,3,6-dianhydromannitol. The observation that the latter is not identical with isomannide eliminates this structure and leaves only [CONTRIBUTION FROM
THE
939
ISOSORBIDE
the 1,4,3,6-dianhydromannitolstructure for isomannide. cmBRIDGE,M~~~~~~~~~~~ RECEIVED JANUARY 29, 1946
DEPARTMENT OF CHEMISTRY, MASSACHUSETTS INSTITUTEOF TECHNOLOGY, AND FROM RESEARCH DEPARTMENT, ATLAS POWDER COMPANY]
Hexitol Anhydrides.l
THE
1,4,3,6-Dianhydro-~-iditol and the Structures of Isomannide and Isosorbide
BY HEWITTG. FLETCHER, J R . , ~AND R. MAXGOEPP, JR.~ HzC-1 The ring structure of. isomannide has recently I been determined independently by the present HCOH c=o c=o authors with their collaborators3 and by Wiggims8 I O I O I O as 1,4,3,6. The closely analogous substance, T C H o--FH isosorbide, was shown by Hockett. Fletcher, HCH L HC---I Sheffield and Goepp4 to contain the same ring system. The present research provides indeH+oH +=o k=o I pendent and conclusive proof of the correctness of -C& I-CHZ C -H 'I these structure assignments and has also resulted 1,4,3,6-Di1,4,3,6-Di1,4,3,6-Diin the characterization of a new dianhydrohexianhydroanhydro-n-threoanhydrotol, 1,4,3,6-dianhydro-~ iditol. L-sorbose 2,5-diketohexitol D-fructose Comparison of the structures of isosorbide and The dehydrogenating properties of the catalysts isomannide shows that they are identical save for the configuration of the second carbon atom. usually employed for hydrogenation are well Partial oxidation of isosorbide would produce known. With this fact in mind a suspension of 1,4,3,6-dianhydro-~-fructose, 1,4,3,6-dianhydra8-~-Raney nickel in molten isosorbide was heated at 140' in vacuo (2 mm.) for a brief period. Subsesorbose or 1,4,3,6-dianhydro-~-threo-2,5-diketohexitol. Isoniannide, because of its end-to-end quent treatment of the mixture of sirup and catasymmetry would yield only the first and the third lyst a t 190 to 200' under a pressure of 3750 pounds of these compounds. Subsequent reduction of per square inch of hydrogen was, indeed, found 1,4,3,6-dianhydro-~-fructose would presuma'bly to produce an amorphous mixture which, unlike give rise to a mixture of isomannide and iso- isosorbide, could not be induced to crystallize. sorbide ; reduction of 1,4,3,6-dianhydro-~-sorboseComplete benzoylation of this sirup and fractional would lead to isosorbide and 1,4,3,6-dianhydro-~- crystallization of the resulting mixture gave a iditol, while reduction of 1,4,3,6-dianhydram-~- well-defined crystalline substance having the threo-2,5-diketohexitol would result in the forma- analysis of a dianhydrohexitol dibenzoate. It proved to be unlike the dibenzoate of either isotion of a mixture of all three dianhydro-hexitols. sorbide or isomannide and apparently one or both of two changes had taken place during the treatment of isosorbide. Either isomerization had HOCH HOCH altered the ring structure of the isosorbide to a C' T o-HoJ I o r F H IJ form more stable under the rather drastic conditions of the experiment, or inversion of one or more of the hydroxyl groups, as pictured above, had taken place. The latter hypothesis indicated that O H !: the crude isomerizate might contain, along with E ! H CHa D OCHzH L-CHz unchanged or reformed isosorbide, isomannide 1,4,3,6-Di1,4,3,6-Di1,4,3,6-Diand the new hexide 1,4,3,6-dianhydro-~-iditol. anhydroanhydroanhydroActually, chromatography of the crude isomeriD-mannitol L-iditol D-sorbitol (isomariiiide) (isoidide) zate in another laboratory demonstrated the ~ (isosorbide) presence of three compounds.b ( I ) The previous paper of this series, THISJOURNAL, 66, 937 (1946). See also Fletcher and'Goepp, ibid., 87, 1042 (1945). It is obvious that if this isomerization involves (2) Present addresses: Hewitt G. Fletcher, Jr., Division of Chemsimply inversion of the hydroxyl groups in isoistry, National Institute of Health, Bethesda 14, Md.; R. M a x Goepp, Jr., Research Department, Atlas Powder Company, W 1 1 - sorbide, a similar isomerizate, containing the same new dianhydrohexitol, should be obtained mington 99. Del. ( 3 ) Hockett, Fletcher, Sheffield, Goepp and Soltzberg. 'Tms by a similar treatment of isomannide. A parallel JOURNAL, 68, 930 (1946); Hockett and Sheffield, i b i d . . 68,937 (1046); hydrogenation of isomannide was therefore run Wiggins, J . Chem, Soc., 4 (1945). (4) Hockett, Fletcher, Sheffield and Goepp. THISJOURNAL, 68, and yielded a sirupy mixture from which the new
1
I I
1
Hz7-l1
Hz7-l
1
r--7H I
Hz'-l Hz71 or+yo
1
927 (1946).
(6) Lew, Wolfrom and Goepp. aid, ET, 1866 (1945).
